title: Regulation of ENaC expression at the cell surface by Rab11.
abstract: The epithelial Na(+) channel (ENaC) is an essential channel responsible for Na(+) reabsorption. Coexpression of Rab11a and Rab3a small G proteins with ENaC results in a significant increase in channel activity. In contrast, coexpression of Rab5, Rab27a, and Arf-1 had no effect or slightly decreased ENaC activity. Inhibition of MEK with PD98059, Rho-kinase with Y27632 or PI3-kinase with LY294002 had no effect on ENaC activity in Rab11a-transfected CHO cells. Fluorescence imaging methods demonstrate that Rab11a colocalized with ENaC. Rab11a increases ENaC activity in an additive manner with dominant-negative dynamin, which is a GTPase responsible for endocytosis. Brefeldin A, an inhibitor of intracellular protein translocation, blocked the stimulatory action of Rab11a on ENaC activity. We conclude that ENaC channels, present on the apical plasma membrane, are being exchanged with channels from the intracellular pool in a Rab11-dependent manner.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Karpushev
authors.affiliation: Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Levchenko
authors.affiliation: Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
authors.forename: Tengis S
authors.initials: TS
authors.lastname: Pavlov
authors.affiliation: Biotechnology & Bioengineering Center, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
authors.forename: Vy
authors.initials: V
authors.lastname: Lam
authors.affiliation: Biotechnology & Bioengineering Center, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
authors.forename: Kalyan C
authors.initials: KC
authors.lastname: Vinnakota
authors.affiliation: INSERM, U773, Centre de Recherche Biomedicale Bichat-Beaujon CRB3, Universite Paris, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Vandewalle
authors.affiliation: Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA; Biotechnology & Bioengineering Center, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Wakatsuki
authors.affiliation: Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA; Kidney Disease Center, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA. Electronic address: Staruschenko@mcw.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Staruschenko
mesh_terms: D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D051379:Mice; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020826:rab3A GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D053503:Epithelial Sodium Channels; D020691:rab GTP-Binding Proteins; D020826:rab3A GTP-Binding Protein; D000099193:rab11 GTP-Binding Proteins